Structural and mechanistic insights into regulation of HBO1 histone acetyltransferase activity by BRPF2

Ye Tao; Chen Zhong; Junjun Zhu; Shutong Xu; Jianping Ding

doi:10.1093/nar/gkx142

Structural and mechanistic insights into regulation of HBO1 histone acetyltransferase activity by BRPF2

Nucleic Acids Res. 2017 Jun 2;45(10):5707-5719. doi: 10.1093/nar/gkx142.

Authors

Ye Tao¹, Chen Zhong¹, Junjun Zhu¹, Shutong Xu¹, Jianping Ding^{1

2

3

4}

Affiliations

¹ National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, and University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
² School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.
³ Shanghai Science Research Center, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China.
⁴ Collaborative Innovation Center for Genetics and Development, Fudan University, 2005 Songhu Road, Shanghai 200438, China.

Abstract

HBO1, a member of the MYST family of histone acetyltransferases (HATs), is required for global acetylation of histone H3K14 and embryonic development. It functions as a catalytic subunit in multisubunit complexes comprising a BRPF1/2/3 or JADE1/2/3 scaffold protein, and two accessory proteins. BRPF2 has been shown to be important for the HAT activity of HBO1 toward H3K14. Here we demonstrated that BRPF2 can regulate the HAT activity of HBO1 toward free H3 and H4, and nucleosomal H3. Particularly, a short N-terminal region of BRPF2 is sufficient for binding to HBO1 and can potentiate its activity toward H3K14. The crystal structure of the HBO1 MYST domain in complex with this segment of BRPF2 together with the biochemical and cell biological data revealed the key residues responsible for the HBO1-BRPF2 interaction. Our structural and functional data together indicate that the N-terminal region of BRPF2 plays an important role in the binding of HBO1 and a minor role in the binding of nucleosomes, which provide new mechanistic insights into the regulation of the HAT activity of HBO1 by BRPF2.

MeSH terms

Acetylation
Amino Acid Motifs
Binding Sites
Chromatin / chemistry
Chromatin / metabolism
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
HEK293 Cells
Histone Acetyltransferases / chemistry*
Histone Chaperones
Histones / genetics*
Histones / metabolism
Homeodomain Proteins / chemistry
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Models, Molecular
Nuclear Proteins / chemistry
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Nucleosomes / genetics
Nucleosomes / metabolism
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Processing, Post-Translational*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Substrate Specificity
Transcription, Genetic
Tumor Suppressor Proteins / chemistry
Tumor Suppressor Proteins / genetics*
Tumor Suppressor Proteins / metabolism

Substances

Chromatin
Histone Chaperones
Histones
Homeodomain Proteins
JADE1 protein, human
Nuclear Proteins
Nucleosomes
Protein Isoforms
Recombinant Proteins
Tumor Suppressor Proteins
BRD1 protein, human
Histone Acetyltransferases
KAT7 protein, human